Chloroquine does not inhibit SARS-CoV-2 spread in human lung cells: Study - Down To Earth Magazine

The drug stops the spread of the virus that causes COVID-19 in African green monkey kidney cells, but is ineffective in human lung cells

The absence of a vaccine or permanent cure for the novel coronavirus disease (COVID-19) has prompted a global search for a preventive cure, with chloroquine — a drug used to treat malaria — taking the lead and spurring countries to stock the medicine.

Chloroquine has also often been touted by world leaders, including United States President Donald Trump — who said in May 2020, that he was taking the drug as a preventive measure — and Brazilian President Jair Bolsonaro.

In March, the Indian Council of Medical Research — India’s top medical body — gave its assent for using the drug under exceptional circumstances for patients who are at high risk from the disease.

If a recent study is to be believed, however, chloroquine has been found ineffective as a preventive cure.

Researchers at the Infection Biology Unit of the German Primate Center (DPZ) at Leibniz Institute for Primate Research in Göttingen and at the Charité in Berlin, Germany, in fact, advised against using the drug for treating COVID-19.

While chloroquine inhibited the virus infection in African green monkey kidney cells, the drug did not curb the spread of the SARS-CoV-2 virus — that causes COVID-19 — in human lung cells.

“The anti-viral activity of chloroquine is cell type-specific and does not block the infection of lung cells,” said Stefan Pöhlmann, head of the Infection Biology Unit at DPZ.

“This means care should be taken for using relevant cell lines to not waste unnecessary time and resources in our search for testing effective COVID-19 therapeutics,” he added.

The SARS-CoV-2 virus uses two different routes to enter cells, explained a July 22 press release from DPZ, quoting their study.

One route is for the virus to fuse directly with the plasma membrane of the cell and, in turn, introduce its genetic material to the host cell.

Another route is for the virus to reach the interior of the cells upon uptake through endosomes (transport structures).

The viral spike protein of the SARS-CoV-2, in both cases, is responsible for its attachment to cells. This spike protein uses two types of enzymes to activate itself: Cathepsin L (found in endosomes) and TMPRSS2 (on cell surfaces).

The activation can be done either by both or one of the enzymes.

Chloroquine — in the monkey cells — inhibits the virus’ entry, most likely by blocking Cathepsin L, the study showed. The exact manner with which chloroquine blocks the entry of the virus, however, was not clear, said the DPZ press release.

This raised the question of whether the drug also inhibited the infection of lung cells that mostly produce TMPRSS2, with a small quantity of Cathepsin L.

The study, however, showed chloroquine did not stop SARS-CoV-2 from entering human lung cells and spreading there.

“COVID-19 is primarily caused by the infection of lung cells. For this reason, these cells should be given priority in efficacy tests,” said Pöhlmann.

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2020-07-24 11:55:36Z
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